The transformation of 17-keto steroids to corticoids is well known to those skilled in the art. Numerous routes have been utilized. See, for example, U.S. Pat. Nos. 4,041,055, 4,216,159, 4,342,702 and 4,411,835.
The addition of an .alpha.-nitrile anion to ketones has been reported, see Synthesis 92 (1975), including 17-keto steroids, see J. Org. Chem. 43, 4374 (1978). The J. Org. Chem. 43, 4374 (1978) publication discloses the addition of the lithiated mono anion of 3-unsubstituted propionitrile to a 17-keto steroid to give a 17.beta.-hydroxy-17.alpha.-substituted steroid which upon dehydration with thionyl chloride gives a 20-cyano-.DELTA..sup.17 (.sup.20)-steroid, however the oxidation of these 20-cyano-.sup.17 (.sup.20) steroids to 17.alpha.-hydroxy 20-keto steroid does not work well, see J. Org. Chem. 44, 702 (1979). The -OR.sub.21 substituent permits efficient oxidation of the 20-cyano-.DELTA..sup.17 (.sup.20)-steroid (III) to the corticoid (IV). The addition of a .beta.-mettalo-.alpha.-substituted propionitrile to a 17-keto steroid has not been reported. It is surprising and unexpected that the .alpha.-metallo-.beta.-metalloxypropionitrile dianion (V) adds to the 17-keto steroid (I) without elimination of the -OR.sub.21 .alpha. substituent.
The oxidation of 21-acetoxy-.DELTA..sup.17 (.sup.20)-20-cyanopregnanes to the corresponding 17,21-dihydroxy-20-keto steroid derivatives is well known in the steroid literature, see J. Am. Chem. Soc. 76, 5031 (1954); J. Am. Chem. Soc. 70, 1454 (1948); J. Am. Chem. Soc. 71, 2443 (1949); J. Am. Chem. Soc. 77, 196 (1955); Helv. Chim. Acta 34, 359 (1951); and J. Org. Chem. 44, 702 (1979).
The process of the present invention transforms the 17-keto steroid (I) starting materials to the corresponding corticoid (IV) products in only four steps.